April 22, 2009

I would like to direct the readers here to the excellent project-and-career story from Bruce Maryanoff in the most recent J. Med. Chem ASAP. It is very illuminating on how the drug discovery and development works, and it describes in some detail what a bright chemist can hope to achieve in this profession -with the necessary motivation and a decent employer (and tremendous amounts of luck).

It is also an illuminating story on how the process does not work. For example, the currently most popular, target-driven rational-design-based approach can be pretty futile in CNS drug projects . The author also suggests that the management mantra about focusing on the discovery of the next “blockbuster drug” actually bankrupts the industry – financially and scientifically; his drug Topiramate (which has been making 2 billions a year for the company) would have not been discovered or developed under the management methods currently prevalent in the industry. Few things stand out: 1) It seems that having a blind luck and testing the compounds in a realistic animal model is more important than having a correct mechanistic understanding how the drug candidate actually works. 2) Few independent-minded individuals in their pharmacology and chemistry have made a good use of their lucky break. They stubbornly kept the research program going – even as their managers were lukewarm and would not support the compound development for a long time. It also goes to the credit of the management that allowed their researchers to pursue this as their hobby. The story shows that the progress in pharma research does not really happen by imposing some management-theory-derived reporting structure on the research department, by drafting the flowcharts and aligning the teams. For medchem research to succeed, the projects should be allowed to self-organize around the bright individuals rather than being planed out from top down, with red tape and micromanagement.

In this context it is entertaining to read rather disingenuous remarks made by the Merck chief strategy officer Merv Turner at the pharma management conference. He explained that they are currently sacking lots of people in research because “Seventy-five cents of every dollar we spend on R&D goes to fund failure” and “the future results must come at a lower cost”.

The actual drug discovery cost makes only few percent of the final drug development cost. By far the most expensive part is the clinical trials and namelly the late-stage clinical trials. What the Merck management poseurs do not tell in public is that it was the Merck top management decisions that cemented their company’s commitment to these “the next blockbuster” projects – which eventually led to a string of stunningly expensive late-stage failures. When the top executives receive massive stock option bonuses, they become mercenaries of the stock prices. Their wishful thinking baloney percolates from top down through the management layers, etc.

There are many parallels between the state of pharma industry and the recent financial sector collapse, and it is always the executives who run their companies to the ground that are rewarding themselves most obscenely. Remember this whenever the pharma companies claim that the freedom to price their drugs is essential for the innovation.

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Update: Here are additional two greatarticles from Bruce Maryanoff on the subject